AB0406 EFFICACY OF TNF-ALPHA INHIBITORS IN MANAGEMENT OF IMMUNE CHECKPOINT INHIBITOR RELATED ARTHRITIS
Authors: M. Callan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Use of immune checkpoint inhibitors (ICI) has revolutionised management of multiple malignancies but may be complicated by development of immune-related adverse events including inflammatory arthritis. Once triggered, arthritis may persist, with 50% patients having ongoing symptoms even 1 year after stopping ICI treatment. EULAR guidance, based on small retrospective and prospective studies and case reports, recommends treatment with corticosteroids, with escalation to DMARDs particularly where arthritis remains active at doses of prednisolone &gt;10mgs [1]. There is some evidence to support use of biologic DMARDs in management, but a lack of studies using validated rheumatology scoring tools to objectively assess ICI arthritis response to biologic agents [2-4]. <h3>Objectives</h3> The aim of this study was to assess efficacy of TNF-alpha inhibitors in ICI arthritis, using change in Clinical Disease Activity Index (CDAI) as an outcome measure. The CDAI was chosen as it is independent of ESR and CRP which may be influenced by other complications of malignancy and its treatment. <h3>Methods</h3> This was a single centre retrospective study of 65 patients referred with musculoskeletal symptoms following use of an ICI. Patients with ICI arthritis treated with a TNF-alpha inhibitor were identified and their notes systematically reviewed for information about malignancy diagnosis, use of ICI, presentation with inflammatory arthritis and its response to treatment, with arthritis activity monitored using the CDAI. <h3>Results</h3> 40 of the 65 patients referred presented with an inflammatory arthritis and 9 were treated with a TNF-alpha inhibitor to manage arthritis. These included 4 male and 5 female patients, with mean age 65 years. 5 patients had melanoma, 2 renal cell cancer, 1 mesothelioma and 1 gall bladder adenocarcinoma. All 9 patients had received treatment with a PD-1/PDL-1 inhibitor, with 5 patients also receiving a CTLA-4 inhibitor. 1 patient had a prior diagnosis of psoriatic arthritis and 1 had a prior diagnosis of rheumatoid arthritis. Both experienced increased arthritis activity following ICI treatment. The remaining 7 patients developed new onset polyarthritis following ICI treatment, with 1 of 7 being anti-CCP and RF positive. Prior to use of a TNF-alpha inhibitor, all 9 patients had received treatment with prednisolone. 4 patients had been treated with methotrexate, of whom 3 had also had sulfasalazine. 6 of 9 patients received adalimumab as a first biologic, with the other 3 receiving infliximab. CDAI prior to use of a TNF-alpha inhibitor ranged from 20 to 62, with a mean of 32.8. 2 patients had moderate disease activity (CDAI&gt;10 and ≤22) and 7 patients had high disease activity (CDAI&gt;22). The CDAI at follow up ranged from 4 to 31 with a mean of 13.2. 5 patients had low disease activity (CDAI≤10), 4 patients had moderate disease activity and 2 patients had high disease activity at this time. Use of a TNF-alpha inhibitor was associated with a clinically meaningful improvement in CDAI in 8 of 9 patients at follow up after a mean of 11 weeks of treatment, including 1 patient who continued with ICI treatment. <h3>Conclusion</h3> This single centre retrospective study suggests efficacy of TNF-alpha inhibitors in management of ICI arthritis. Similar to previous work, this study is small and limited by lack of a control cohort but has the advantage of using a validated rheumatology scoring tool to confirm changes in arthritis activity. TNF-alpha inhibitors have a shorter time to onset of action than csDMARDs and so offer an opportunity for early control of ICI arthritis, with potential for use in parallel with continued ICI treatment if needed for management of the underlying malignancy. <h3>References</h3> [1] Kostine et al Ann Rheum Dis 2021 80:36 [2] Jensen et al Biomed Pharmacotherapy 2022 148:112687 [3] De La Fuente et al RMD Open 2022 8(2):e002612 [4] Holmstroem et al J Immunother Cancer 2022 10:e005111 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.